Core Insights - Upstream Bio, Inc. presented additional data from the Phase 2 VIBRANT clinical trial for verekitug, showing significant efficacy in treating chronic rhinosinusitis with nasal polyps (CRSwNP) [1][2] - The trial demonstrated a placebo-adjusted reduction in endoscopic nasal polyp score (NPS) of -1.95 (p < 0.0001) and a reduction in nasal congestion score (NCS) of -0.96 (p < 0.0001) [1][2] - The company plans to initiate Phase 3 trials for CRSwNP and severe asthma, highlighting verekitug's potential to improve treatment standards for serious respiratory diseases [2][3] Company Overview - Upstream Bio is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases, particularly severe respiratory disorders [11] - Verekitug is a novel monoclonal antibody targeting the thymic stromal lymphopoietin (TSLP) receptor, which plays a key role in inflammatory responses [8][11] - The company aims to address unmet needs in patients with conditions like CRSwNP and severe asthma through innovative therapies [11] Clinical Trial Details - The VIBRANT trial was a global, randomized, double-blind, placebo-controlled study involving 81 adults with CRSwNP, assessing the efficacy and safety of verekitug over 24 weeks [7] - Participants received 100 mg of verekitug or placebo every 12 weeks, with primary and secondary endpoints focused on nasal polyp scores and other symptoms [7] - The trial's design and endpoints are intended to support future regulatory submissions for product approval [3][7] Efficacy and Safety - Verekitug reduced the need for surgery or systemic corticosteroids by 76% (p = 0.03) compared to placebo, indicating a strong therapeutic effect [1][2] - The treatment was generally well tolerated, with no serious adverse events (SAEs) reported, reinforcing its favorable safety profile [1][2] Future Directions - Upstream Bio is preparing to initiate registrational trials for verekitug in CRSwNP and severe asthma, following planned interactions with regulatory authorities [3] - The company believes verekitug's unique mechanism of action and dosing schedule could significantly enhance the standard of care for patients with serious respiratory diseases [2]

2026 J.P. Morgan Healthcare Conference Rand Sutherland, MD, Chief Executive Officer January 2026 © 2026 Upstream Bio, Inc. No Image Disclaimer This presentation contains forward-looking statements of Upstream Bio, Inc. ("Upstream," "the Company," "we," "us," or "our") that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operations, business strategy ...

VIBRANT Phase 2 Study Results - The Phase 2 VIBRANT study of verekitug in CRSwNP met the primary endpoint, demonstrating a statistically significant reduction in Nasal Polyp Score (NPS) of -1.8 (p<0.0001) [11, 71, 85] - Key secondary endpoints were also met, including a Nasal Congestion Score (NCS) reduction of -0.8 (p=0.0003) [11, 71, 85] and a 76% reduction in the need for surgery or systemic steroids (p=0.03) [11, 71, 85] - Verekitug, dosed every 12 weeks, showed clinical activity at week 24 similar to tezepelumab dosed every 4 weeks [14, 65] - In the VIBRANT trial, 93% of subjects completed the study [38] Safety and Tolerability - Verekitug was generally well tolerated, with no serious adverse events (SAEs) observed [11, 71, 85] - The incidence of adverse events (AEs) was similar across treatment groups, with treatment-emergent adverse events (TEAEs) related to study treatment occurring more frequently in the placebo group [48] Verekitug's Potential - Upstream Bio is developing verekitug as an antagonist of the TSLP receptor, with the goal of achieving rapid, complete, and sustained receptor occupancy for up to 24 weeks after the last dose [21] - Current biologics sales in CRSwNP alone are estimated to exceed $1 billion globally [29] - Upstream Bio is studying verekitug across multiple indications with high unmet need, including severe asthma (VALIANT trial, topline data expected in Q1 2026) and COPD (VENTURE trial, currently enrolling) [22, 23]